1. Field of the Invention
The present invention relates to the production of 3-[2-{(methylsulfonyl)oxy}ethoxy]-4-(triphenylmethoxy)-1-butanol methane sulfonate, more particularly to the preparation of a single optical isomer of the product involving the resolution of a racemic mixture of intermediate products.
2. Prior Art
The production of certain pharmaceuticals involves the use 3-[2-{(methylsulfonyl)oxy}ethoxy]-4-(triphenylmethoxy)-1-butanol methane sulfonate (MTBS). Related compounds to MTBS are disclosed in PCT Publication No. WO 97/19080. Preparation of MTBS and related compounds has traditionally involved using relatively expensive starting materials. Some of these methods are described in Journal of Organic Chemistry, Vol. 63, No. 6, pp. 1961-1973 (1998) and one synthesis route is shown in the following reaction scheme. In this synthesis technique, (R)-glycidol (graphic formula A) is protected with triphenylmethyl (Tr) to yield trityl glycidol (graphic formula B), and the glycidol ring is opened by treatment with vinylmagnesium bromide to produce the ether of graphic formula C. Allylation of compound C produces the ether of graphic formula D. Ozonolysis of compound D followed by subsequent sodium borohydride reduction yields the diol of graphic formula E which is treated with methane sulfonyl chloride (MsCl) to produce (S)-3-[2-{(methylsulfonyl)oxy}ethoxy]-4-(triphenylmethoxy)-1-butanol methane sulfonate (graphic formula F). ##STR1##
This method of producing MTBS is not commercially economical. Accordingly, a need remains for preparing 3-[2-(methylsulfonyl)oxy}ethoxy]-4-(triphenylmethoxy)-1-butanol methane sulfonate which uses readily available and relatively inexpensive starting materials.